The research objectve is to determine those factors that influence the perinatal adjustments related to carbohydrate homeostasis. Hypoglycemia can be associated with clinical manifestations and even death in some newborn infants and with no apparent symptomotology in others. The proposed studies are to extend our knowledge of the pathogenesis of low blood sugar and its relationship to the adaptation and ability to utilize other metabolic substrates in the newborn period. On-going studies have shown that data from multiple animal models can be correlated with those from ethical human investigations to provide a rational basis for understanding the morbidity and mortality associated with alterations in carbohydrate metabolim in the neonate. Thus, regulatory processes, both before and after birth, will be studied in the rat, pig and monkey in order to learn what factors alter these processes. Substrate utilization (e.g. free fatty acids, amino acids, ketone bodies, glycerol), hormones and rate limiting enzyme activities will be correlated throughout development. The discovery of a unique patient with glycerol intolerance has resulted in investigation of the role of glycerol as an energy source and its metabolic pathways of utilization in brain, liver and kidney throughout fetal and neonatal development. The mechanisms responsible for the delayed maturation in glycolysis and alterations in amino acid metabolism associated with intrauterine ketosis in the rat will also be investigated. Alanine and glutamine tolerance tests in both model animals and sick infants will be done to determine the utilization and gluconeogenic potential of these amino acids during stress in early life. Assays of insulin, growth hormone, cortisol and catecholamines will also be done to determine hormonal control and response as well as to provide insights for therapy and management of the high-risk newborn in order that optimal growth and development will ensue. BIBLIOGRAPHIC REFERENCES: Maclaren, N.K., Cowles, C., Ozand, P., Shuttee, R., and Cornblath, M.: Glycerol Intolerance With Hypoglycemia, J. Ped., 86:43, 1975. Ozand, P. T., Stevenson, J.H., Tildon, J.T., and Cornblath, M.: The Effects of Hyperketonemia on Glycolytic Intermediates in the Developing Rat Brain, Neurochem., 25: 61, 1975.